Most of currently promising molecular-targeted drugs against cancer are receptor tyrosine kinase inhibitors such as erlotinib and lapatinib. Many of them are highly effective against cancers with mutation, amplification, or overexpression of target genes. However, such molecular-targeted agents cannot exert efficacy against cancers in which genes that are not their targets are altered. Thus, there is still no established therapeutic method that is effective against such cancers. Inhibitors against novel genes altered in cancer are expected to make a great contribution to treatment of cancer patients on whom conventional drugs have no effect.
Fibroblast growth factor receptors (FGFRs) are kinases belonging to the receptor tyrosine kinase family. FGFR1, FGFR2, FGFR3, and FGFR4 constitute the FGFR family. The ligand is fibroblast growth factor (FGF), and 22 types of structurally similar proteins form a family. It is known that each FGFR is activated upon overexpression, gene amplification, mutation, or translocation, and serves as a cause of cancer. The FGFR signal follows the MAPK pathway or PI3K/AKT pathway. In cancer, the signal is known to be involved in cell growth, angiogenesis, cell migration, invasion, metastasis, and such (Non-patent Document 1).
All such FGFR family kinases have been strongly suggested to be associated with cancer; it is thought that inhibition of these FGFR family kinases in cancer tissues can be a promising therapy for the above-mentioned cancer types.
In this context, Applicants have already provided low-molecular-weight compounds that can inhibit fibroblast growth factor receptor (FGFR) family kinases in cancer tissues (Patent Document 1).
When providing pharmaceuticals, formulations must, for example, be effectively absorbed within the body. Thus, even pyrazole compounds described in Patent Document 1 must be effectively formulated. For example, of formulation forms, encapsulated formulations are administered after enclosing active ingredients (drug substances) in a small space, and therefore, it is important that drug substances are dispersed after capsule disintegration.